Are some of the soluble mediators of the immune response (interferons) responsible for the cognitive, performance, and affective deficits that occur with both acute and chronic virus infections? In the current proposal, we will complete the background parametric studies which will enable us to develop and test an animal model in which we can study the cognitive and performance aspects of the above question. Interferons are responsible for the unpleasant malaise felt during virus infections. They have been administered to humans as treatment for cancer and found to produce neuropsychological effects, thus, they are a good candidate for the cause of the affective and cognitive deficits seen with acute (e.g. colds and flu) and chronic (e.g. Epstein-Barr virus and Human Immunodeficiency Virus) viral infections. In present grant, we propose to determine the type of interferon, dose, route and schedule of injection to use in a mouse model for the human response to interferon. Using this information, we will establish whether rodents show the same effects as humans. Specifically, we will determine whether mice show rises in temperature, decreases in activity and food and water intake, nausea, fatigue and incoordination. These studies will, in addition, provide us with information we will need to design studies which probe the cognitive effects of interferon, and the mechanisms by which interferon has its effects upon the brain.